Virilization

VirilizationClinical features associated with a high level of

male hormones in women.• Hirsuitism• Acne• Deepening of voice • Increased muscle mass• Breast atrophy

Hirsutism• Excessive growth of thick terminal hair in a male

distribution in women (upper lip, chin, chest, back, lower abdomen, thigh, forearm)

• Most common presentation of endocrine disease.

• DD: Hypertrichosis, which is generalised excessive growth of vellus hair.

• The aetiology is androgen excess

Androgens and Hirsuitism

• Hirsutism can be caused by either an increased level of androgens or an oversensitivity of hair follicles to androgens.

• Testosterone stimulates hair growth, (size, intensity of growth and pigmentation).

obesity/insulin and Hirsuitism

• High circulating levels of insulin are implicated in women for the development of hirsutism.

• Obese (insulin resistant hyperinsulinemic) women are at high risk of becoming hirsute.

• Treatments that lower insulin levels lead to a reduction in hirsutism.

• High concentration of insulin (directly and through IGF I) is thought to stimulate theca cells in ovaries to produce androgens.

Hirsuitism: Causes

• Idiopathic• Polycystic ovarian syndrome• Congenital adrenal hyperplasia• Exogenous androgen administration• Androgen-secreting tumour of ovary or

adrenal cortex

Hirsuitism: Idiopathic

• Often familialMediterranean or Asian background

• Investigations: normal

• Treatment: –Cosmetic measures–Anti-androgens

Hirsuitism: PCOS• Aetiology -poorly understood• Constellation of clinical and biochemical

features of varying severity –Obesity–Oligomenorrhoea/ Secondary amenorrhoea– Infertility –multiple cysts in the ovaries

Hirsuitism: PCOS

Mechanisms* ManifestationsPituitary dysfunction High serum LH

High serum prolactin

Anovulatory menstrual cycles

OligomenorrhoeaSecondary amenorrhoeaCystic ovariesInfertility

Androgen excess HirsutismAcne

Obesity HyperglycaemiaElevated oestrogens

Insulin resistance DyslipidaemiaHypertension

Hirsuitism: PCOS

• Investigations: LH:FSH ratio > 2.5:1

Minor elevation of androgensMild hyperprolactinaemia

• Treatment Weight loss

Cosmetic measuresAnti-androgensInsulin-sensitising drugs

Hirsuitism: Congenital adrenal hyperplasia

• 95% 21-hydroxylase deficiency• Clinical Features: –Pigmentation–History of salt-wasting in childhood–Ambiguous genitalia –Adrenal crisis when stressed

Hirsuitism: Congenital adrenal hyperplasia

• Investigations– Elevated androgens, suppressible with

dexamethasone –Abnormal rise in 17OH-progesterone with ACTH

• Treatment –Glucocorticoid replacement administered in

reverse rhythm to suppress early morning ACTH

Hirsuitism: Exogenous androgens• Athletes

Virilised• Investigations:– Low LH and FSH–Analysis of urinary androgens may detect

drug of misuse• Treatment:– Stop steroid misuse

Hirsuitism: Androgen-secreting tumour ovary or adrenal cortex

• Rapid onset virilisation: – clitoromegaly –deep voice–balding –breast atrophy

Hirsuitism: Androgen-secreting tumour ovary or adrenal cortex

• Investigations: – High androgens which do not suppress with

dexamethasone or oestrogen– Low LH and FSH– CT or MRI usually demonstrates a tumour

• Treatment: – Surgical excision

Hirsuitism : Clinical approach• The severity of hirsutism is subjective• Important observations are –– Drug and menstrual history – Calculation of BMI –Measurement of BP – Examination for virilisation (clitoromegaly, deep

voice, male-pattern balding, breast atrophy) – Acne vulgaris– Cushing's syndrome

• When recent & with virilisation, suggestive of a rare androgen-secreting tumour

Hirsuitism:Investigations

Random blood sampling for testosterone, prolactin, LH and FSH

Hirsuitism:Investigations

• Random blood – testosterone, Prl, LH and FSH. • If Cushingoid features +: Overnight 1 mg Dexa

suppression test

Hirsuitism:Investigations

• Random blood – testosterone, Prl , LH and FSH. • If Cushingoid : Overnight 1 mg DST• If testosterone levels are high (with low LH &

FSH): look for source of excess androgen

Hirsuitism:Investigations

• Random blood – testosterone, Prl , LH and FSH. • If Cushingoid : Overnight 1 mg DST• If testosterone high (with low LH & FSH): ? source• Suspected CAH (21-hydroxylase deficiency): short

ACTH stimulation test, with measurement of 17OH-progesterone

Hirsuitism: Investigations

• Androgen-secreting tumours: Testosterone is not suppressible by –Dexamethasone• Overnight or • 48-hour low-dose suppression test

–Oestrogen (30 μg / day X 7 days)

• CT or MRI of the adrenals and ovaries

Hirsuitism: Treatment• Cosmetic measures - shaving, bleaching and

waxing • Electrolysis and laser treatment : for small areas

• Eflornithine cream : Inhibits ornithine decarboxylase in hair follicles & may reduce hair growth

Hirsuitism: Treatment• Weight reduction for obese patients with PCOS –enhances insulin sensitivity – reduces the peripheral conversion of androgens

by adipose tissue – reduces metabolic clearance of cortisol, thereby

reducing ACTH-dependent adrenal androgen secretion

Hirsuitism: TreatmentIf these conservative measures have failed- • Anti-androgen therapy The life cycle of hair follicles is at least 3 months,

so no improvement is likely before this. Only replacement hair growth is suppressed.

• Insulin-sensitising drugs (thiazolidinediones and biguanides)

Have a role but unless the patient has lost weight, the hirsutism will return once discontinued.

ANTI-ANDROGEN THERAPY• Androgen receptor antagonists–Cyproterone acetate– Spironolactone

• 5 α-reductase inhibitors (prevents conversion of testosterone to active form)- – Finasteride

• Suppress ovarian steroid production and elevate SHBG (sex hormone-binding globulin )– Oestrogen (+ Cyproterone acetate)

• Suppress adrenal androgen production- –Glucocorticoids